JP-2022510454-A5 -

Dates

Publication Date

20221214

Application Date

20191204

Description

If visual inspection indicates that crystalline iloperidone is completely suspended, the suspension may be left to stand for 15 minutes. After 15 minutes, the suspension may be gently redispersed, for example, by slowly inverting the vial for 10 to 15 seconds without stirring, vortexing, manual mixing, or shaking. Regardless of whether any 15-minute standing period and subsequent gentle redispersion step have been performed following the suspension of crystals in the medium, the dosage of the suspension may be immediately drawn into a syringe for administration to the subject. In a method including any 15-minute standing period and gentle redispersion step, the dosage of the suspension may be drawn into a syringe, for example, within about 20 seconds after the completion of the gentle redispersion step. While various embodiments are described herein, those skilled in the art will understand from the specification that various combinations, modifications, or improvements of elements may be made within the scope of the invention. Furthermore, many modifications can be made to adapt the disclosure of the invention to specific circumstances or materials without departing from the main scope of the invention. Thus, the invention is not limited to the specific embodiments disclosed, but is intended to encompass all embodiments within the scope of the appended claims. The embodiments of the present invention include the following: <1> The process includes combining crystalline iloperidone with a suspension medium, wherein the crystalline iloperidone is present in the suspension medium at a concentration of 166.67 mg to 200 mg per 1 mL of the medium solution. A method for preparing an injectable, long-acting formulation of crystalline iloperidone. <2> The method according to <1>, wherein the amount of crystalline iloperidone to be combined with the suspension medium is approximately 600 mg. <3> The method according to <1>, wherein the amount of the suspension medium to be combined with the crystalline iloperidone is approximately 3.0 mL to approximately 3.6 mL. <4> The method according to <1>, characterized by a Dv50 of crystalline iloperidone having a particle size of approximately 120 μm or less. <5> The method according to <4>, characterized by a Dv50 having a particle size of approximately 91 μm to approximately 118 μm of crystalline iloperidone. <6> The method according to <5>, characterized by a Dv50 having a particle size of approximately 98 μm to approximately 105 μm of crystalline iloperidone. <7> The method according to any one of <1> to <6>, wherein the suspension medium comprises Poloxamer 188, carboxymethylcellulose (CMC) sodium, mannitol, and water. <8> The method according to <7>, wherein the suspension medium comprises 4.00 mg of Poloxamer 188, 14.00 mg of carboxymethylcellulose (CMC) sodium, 90.00 mg of mannitol, and an appropriate amount of water up to 2 mL per 2 mL of the suspension medium. <9> The method according to any one of <1> to <6>, further comprising combining the crystalline iloperidone with the suspension medium and then suspending the crystalline iloperidone in the suspension medium by stirring, vortexing, or shaking. <10> The method according to <9>, further comprising allowing the suspension to stand for 15 minutes following the suspension. <11> The method according to <10>, further comprising gently redispersing the suspension after the 15 minutes have elapsed. <12> The method according to <9>, further comprising drawing a dose of the suspension into a syringe for administration. <13> The method according to <11>, further comprising drawing a dose of the suspension into a syringe within 20 seconds of the redispersion. <14> The process further includes removing excess suspension and air bubbles from the syringe, wherein after the removal step, the amount of to be administered is approximately 2.5 mL to approximately 3.0 mL. The method described in <12> or <13>. <15> The method according to <14>, wherein the dose of crystalline iloperidone contained in the aforementioned injection volume is approximately 500 mg. <16> The process further includes removing excess suspension and air bubbles from the syringe, wherein after the removal step, the amount of to be administered is approximately 1.25 mL to approximately 1.5 mL. The method described in <12> or <13>. <17> The method according to <16>, wherein the dose of crystalline iloperidone contained in the aforementioned injection volume is approximately 250 mg. <18> A method for administering an injectable, long-acting formulation of crystalline iloperidone suspended in a medium, This includes intramuscular injection of the sustained-release formulation using a syringe within a time of approximately 5 seconds or less. The aforementioned method. <19> The method according to <18>, characterized by a Dv50 of crystalline iloperidone having a particle size of approximately 120 μm or less. <20> The method according to <19>, characterized by a Dv